OPINI

Grape Seed Effects on Blood Pressure and

Plasma Lipid Level
Daniela Angeline,1 Michelle Martina2
1
General Practitioner in Ade Mohammad Djoen General Hospital, Sintang, West Borneo
2
General Practitioner in North Jakarta, Indonesia

ABSTRACT
Grape seed is known for its antioxidative and anti-inflammatory properties. This paper discuss its benefits on human, such as reducing blood
pressure and plasma lipid level, therefore reducing atherosclerosis risk and subsequently prevent cardiovascular diseases.

Keywords: Blood pressure, grape seed, hypertension, plant-derived therapeutics, plasma lipid

ABSTRAK
Biji anggur dikenal karena efek antioksidatif dan anti-inflamasi. Tulisan ini bertujuan untuk menjelaskan komponen dalam biji anggur dan
manfaatnya bagi manusia, seperti efek menurunkan tekanan darah dan kadar lipid plasma, sehingga dapat mengurangi risiko aterosklerosis dan
dapat mencegah penyakit kardiovaskuler. Daniela Angeline, Michelle Martina. Efek Biji Anggur terhadap Tekanan Darah dan Kadar Lipid
Plasma

Kata kunci: Biji anggur, hipertensi, lipid plasma, tekanan darah, terapi dari tumbuhan

BACKGROUND
Cardiovascular diseases (CVDs) is one of the
leading cause of deaths worldwide, causing
approximately 17.9 million deaths in 2016,
or 31% of all deaths globaally.1 Eighty-five
percents of these CVDs deaths are due to heart
attack and stroke.1 Most deaths occured in
low- and middle-income countries as people
are not provided with early detection nor
treatment for risk factors.1 To reduce high level
of circulating lipids and reduce blood pressure,
most physicians will prescribe HMG-CoA
reductase inhibitors and anti-hypertensive
drugs. Various pharmaceutical companies
offer different approaches from conventional
drugs to plant-derived therapeutics. One of
these known plants-derived therapeutics is
grape seed extract. Several in vitro and animal
studies showed that compounds in grape
seed have positive effects in modulating
different factors associated to CVDs. This
paper reviews the human studies of grape
seed extract.
Grape Seed Component and Benefits
Sativa grapes (Vitis vinifera L) has been
worldwide’s interest due to its nutritional
Alamat Korespondensi email: dnl.angie@gmail.com
benefits for human health. Different
components in the grapes have benefits
for health, such as grape seed extract and
also grape skin. Grape seed extract contain
high concentration of polyphenols, mostly
monomeric flavan-3-ols and oligomeric
proanthocyanidins.2 Grape seed has high
antioxidant properties which work by
modulating antioxidant enzyme expression,
therefore lowering the oxidative damage
in cells, works as anti-inflammatory and
anti-atherosclerotic agent.3 Due to its anti-
atherosclerotic effect, grape seed extract
has cardioprotective effect to the heart by
modulating different risk factor contributing to
CVDs such as hypertension and dyslipidemia.
Other proven health benefit antimicrobial and
anticancer properties.4
Grape seeds contain protein (11%), fiber (35%),
minerals (3%), water (7%), and 7 to 20% lipid
content.5 Factors influencing the constituent
of the grape seed includes the type of grape,
ripeness, geographic environment, climate
condition. Different microbiota in different
individual and genetic profile also differs the
bioavailability of grape seed extract.6 The
two most common components produced
are grape seed extract and grape seed oil
according to their manufacturing process.
Grape seed has polyphenol compound which
are mainly flavonoids, monomeric phenolic
compounds such as catechins, epicatechins
and epicatechin-3-O-gallate and dimeric,
trimeric and tetrameric procyanidins.5 The
90% of main polyphenols identified in grape
seed are procyanidins which are the most
interesting constituent found in grape seed
and 7% other polyphenol compounds.3 As this
constituent are very beneficial, researchers
began to search for the main source of
procyanidins in grape, and found that one
of the most concentrated part are inside the
seed of grape.6
Grape seed oil content usually derived from
mechanical extraction or organic solvent. The
oil content of grape seeds are linoleic acid
which belong to the group of polyunsaturated
fatty acid (PUFA) that has been proven to have
a good effect of human health.7 The grape
seed has PUFA ranging from 85%-90% and
also have oleic acid which belong to the group

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monounsaturated fatty acid (MUFA) in lower
quantity.7 Grape seed also have high content
of vitamin E. Grape variety and environmental
cultivation conditions differs the fatty acid
composition and vitamin E content.7
The constituent of grape seed have a broad
range of health benefits. The beneficial effect
of grape seed to minimize the risk factor
of CVDs derived from its antioxidative and
anti-inflammatory properties which can
help to eliminate free radicals and prevent
lipid oxidation and hence will decrease
LDL level and reducing atherosclerosis. In
a study conducted by Cao,8 287 patients
with asymptomatic atherosclerotic plaque
were given 200 mg grape seed daily for 24
months; the carotid intima-media thickness
and carotid plaque was reduced compared to
control and therefore significantly lower CVDs
events. Other mechanism in which grape seed
have cholesterol-lowering effect is by altering
the lipid metabolism process.9 Its ability to
inhibit the pancreatic cholesterol esterase
even has been proven.9 Although weaker than
simvastatin, it can bind to the bile acids so
increases fecal cholesterol excretion and delay
cholesterol absorption by reducing solubility
of cholesterol in micelles.9
High blood pressure has been one of the risk
factor regarding CVDs. Another beneficial
effect of grape seed is to lower the blood
pressure, although it is still debated; a meta-
analysis of 9 randomized control trials (RCT)
including total 298 samples showed that
systolic blood pressure and heart rate was
significantly decreased though it is much less
than the effect of antihypertensive drugs.10
Procyanidins in grape seed directly inhibit
angiotensin-converting enzymes (ACE) and
increase nitric oxide production which helps
lowering blood pressure and promotes
relaxation and dilation of blood vessels.6
Grape Seed Effects on Blood Pressure and
Plasma Lipid Level
Earlier in 2004, Clifton, et al,11 showed that
grape seed extract could produce 1.1%
greater vasodilatation and weak effect of
lowering systolic blood presure compared
to controls, but no difference were found on
lipid level, C-reactive protein (CRP), nitrate
and fibrinolytic - factors contributing to
endothelial inflammation and atherosclerotic
process. Later in 2018, Kim, et al,12 found that a
CDK-276/ vol. 46 no. 5 th. 2019
single dose of grape seed reduces BP (systolic,
diastolic, and mean arterial pressure/MAP) at
rest and during submaximal exercise. Alteration
of blood pressure are minimum around 3–4
mmHg reduction in MAP. In prehypertensive
males in high metabolic situation, a single
dose of grape seed (300 mg) reduces blood
pressure, peripheral vasoconstriction, and
heart’s workload. The hypothesis in this
study is that grape seed enhances O2 delivery
by endothelium-dependent vasodilation
mechanism, as it increase flow – mediated
dilation.12 Unfortunately this study has small
study sample (n=9).
Compared to study by Kim, et al,12, Park, et al,
in 2016 showed that chronic supplementation
(6 weeks) of grape seed (300 mg) also
brought similar blood pressure reducing
effect, specifically in systolic blood pressure,
improved fasting insulin and insulin sensitivity,
but no difference in fasting plasma lipids,
vascular adhesion molecules, nor endothelial
function (measured by flow – mediated
dilation/FMD).13 Another study by Barona,
et al,14 showed that grape seed generated
lower systolic blood pressure (SBP) and higher
FMD responses after 30-days treatment using
freeze-dried grape polyphenolic powder
in men with metabolic syndrome. The
considered difference of grape seed effect on
lowering blood pressure is that Barona, et al,
used higher total phenolic compound (528
mg/day) compared to study by Kim, et al,
(126 mg/day).12,14 But no lipid-lowering effect
found in these studies.
But Ras, et al,15 showed no significant changes
in both systolic and diastolic blood pressure
after consuming 300 mg of grape seed for
8 weeks in pre hypertension and grade I
hypertension, the slight effect on lowering
both systolic and diastolic blood pressure
failed to achieve statistically significant result.
Lipid-lowering effect of grape seed is still
searched, mostly proven in in vitro and
animal studies. Studies of grape seed effect
on human’s plasma lipid level are still lacking.
Sano, et al,16 in 2008 has showed that 200
mg and 400 mg of grape seed consumption
for 6 weeks and 12 weeks could reduce
oxidized-LDL but not to the other plasma
lipid level. The plasma total cholesterol was
increased but not statistically significant. Lipid
lowering effect was also proven in 52 mildly
OPINI
hyperlipidemic patients aged 21-64 years old
with tryglyceride (TG) level of 150-250 mg/
dL and total cholesterol of 200-300 mg/dL.17
In this study, the dose of grape seed extract
was 200 mg per day for 8 weeks. Compared
to control after 8 weeks, they had significantly
reduced level of total cholesterol level, LDL
level, and oxidized LDL level.17 But, TG and
HDL level wasn’t significantly improved.
Discussion
As CVDs burden growing globally, people with
high risk factors were motivated to find better
diet and healthier lifestyle. One of the purpose
is to reduce plasma lipid profile as one of the
atherosclerotic culprit which subsequently
cause CVDs. One of the suggested functional
food is the lipid – lowering effect of grape
seed. This effect is mostly proven in in vitro
setting and animal studies. Studies by Sano, et
al,16 and Razavi, et al,17 showed that grape seed
has significantly lowered human plasma lipid
level. But this effect was not replicated by Park,
et al,13 and Barona, et al.14
Studies by Razavi, et al,17 Sano, et al,16 and Park,
et al,13 include similar group age which are
between 21–64 years old, 30–70 years old, and
25–65 years old, respectively. The exclusion
criteria of those three were also similar such
as having lipid-lowering or antihypertensive
drugs, diabetes, hepatic dysfunction, eating
other health food, but study by Sano, et al,16
did not mention the exclusion of cigarette
smoking even they did mention to include
only healthy subjects. Razavi, et al,17 showed
that grape seed could reduce total cholesterol,
LDL cholesterol, and oxidized-LDL, while study
by Sano, et al,16 could only prove its effect
on oxidized-LDL, and Park, et al,13 showed
no significant changes in plasma lipid level.
Razavi, et al, Sano, et al, and Park, et al, recruited
52, 61, and 36 subjects, respectively.13,16,17
Study sample may contribute to this diffrerent
results and larger study sample could reduce
the bias.
Many other studies also tried to search grape
seed effect on hypertension. Kim, et al,12 and
Park, et al,13 showed that grape seed could
significantly lower blood presure both in
single dose and chronic supplementation,
although in study by Park, et al,13 only systolic
blood pressure was reduced significantly. But
Ras, et al,15 showed only slight not statistically
significant effect of grape seed in reducing
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blood pressure. In these three studies, other
factors that should be considered is sample
variations; Park, et al,12 sample was 29 people
aged 25–65 years old and Ras, et al,15 has
70 participants aged 35-75 years old, both
studies recruited both female and male
gender but only menopausal females were
included in Ras, et al,15 study. Conversely, Kim,
et al,12 include only 9 male younger subjects
aged 20–24 years old. These differences might
attributed to the different results as advancing
age and decreasing level of estrogen in
postmenopausal women could be one of
unmodifiable risk factors of increased blood
pressure.18
All of this varying result was summarized by
meta-analysis by Feringa, et al.10 This meta-
analysis of 9 RCT with total inclusion of 298
samples was to evaluate the effect of grape
seed on cardiovascular risk factors including
systolic blood pressure, diastolic blood
pressure, heart rate, total cholesterol, LDL or
HDL cholesterol, triglycerides, or CRP in human
trial. The 9 RCT included in the study showed
different results. Feringa, et al,10 concluded
that there is a statistically reduced systolic
blood pressure with mean reduction of -1.54
mmHg and this attributed to significantly
reduced heart rate, but this reduction is still
very modest compared to anti-hypertensive
drug. There is no significant grape seed effect
on other factors included in the study such
as total cholesterol, LDL or HDL cholesterol,
triglycerides, or CRP.10
The different results of grape seed extract in
in vitro studies compared to RCT might be
caused by the different dose and study period.
A higher dose of grape seed extract might
be needed to make a significant changes in
human; there are still no established potential
harmful effect of grape seed in human trial.10
Other study was suggested to discover grape
seed effects as an adjuvant to antihypertensive
and antihyperlipidemic therapies to patients
with high risk factors such as metabolic
syndrome. Also, larger randomized controlled
trial of grape seed in human is needed .
Conclusion
Grape seed is beneficial in people with
modifiable risk factors of cardiovascular
diseases, such as hypertension and high
plasma lipid level. Various trial has proven
its effect in lowering systolic blood pressure,
diastolic blood pressure, mean arterial
pressure, and reducing plasma lipid level.
Hopefully grape seed could reduce the
medication burden in people with multiple
co-morbidities, but another bigger study is
needed.

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